rs3810741

chrX-9765909-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000447366.5(GPR143):c.-2-5083G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 878,720 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 37 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., 9 hem., cov: 24)
  • Exomes 𝑓: 0.00010 (0 hom. 28 hem.)
• Consequence: GPR143 ENST00000447366.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.894

Genes affected

GPR143 (HGNC:20145): (G protein-coupled receptor 143) This gene encodes a protein that binds to heterotrimeric G proteins and is targeted to melanosomes in pigment cells. This protein is thought to be involved in intracellular signal transduction mechanisms. Mutations in this gene cause ocular albinism type 1, also referred to as Nettleship-Falls type ocular albinism, a severe visual disorder. A related pseudogene has been identified on chromosome Y. [provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000249 (28/112397) while in subpopulation EAS AF= 0.00661 (23/3479). AF 95% confidence interval is 0.00452. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR143	XM_024452388.2	c.-2-5083G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR143	ENST00000431126.1	c.-3+211G>A		intron_variant		3
GPR143	ENST00000447366.5	c.-2-5083G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.000249 AC: 28 AN: 112349 Hom.: 0 Cov.: 24 AF XY: 0.000232 AC XY: 8 AN XY: 34511

Gnomad AFR AF: 0.000129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000933

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00659

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00113 AC: 4 AN: 3529 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 227

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0180

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000102 AC: 78 AN: 766323 Hom.: 0 Cov.: 12 AF XY: 0.000151 AC XY: 28 AN XY: 185819

Gnomad4 AFR exome AF: 0.000547

Gnomad4 AMR exome AF: 0.000127

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00300

Gnomad4 SAS exome AF: 0.0000940

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000248

GnomAD4 genome AF: 0.000249 AC: 28 AN: 112397 Hom.: 0 Cov.: 24 AF XY: 0.000260 AC XY: 9 AN XY: 34569

Gnomad4 AFR AF: 0.000129

Gnomad4 AMR AF: 0.0000932

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00661

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000495

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	14
Dann	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3810741; hg19: chrX-9733949;